Influence of Caloric Restriction and Resveratrol in the Sirtuin System in Women and Men Aged 55 to 65 Years

Study Description

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

Women have a natural protection that gives them greater longevity. One hypothesis most commonly used is the estrogen protection in the premenopausal period. However many studies of various forms of hormone replacement therapy proved ineffective in promoting additional protection for women. Thus, it is discussed other ways of protection associated with longevity in women. Of these, the sirtuin system was found in several animal studies to be associated with longevity. This system also showed, through the involvement of several metabolic pathways, an important protection against the process of atherosclerosis. But the activity of this system in humans is unknown and if it is more active in women than in men. The study's main objectives are to analyze this system in healthy 24 women and 24 men aged 55 to 65 years, and their influence on the main metabolic pathways related to longevity and the process of atherosclerosis. The research protocol includes analysis of the influence of sirtuin (SIRT1) in vascular reactivity, lipid profile, antioxidant capacity, markers of inflammation and homeostasis, before and after the interventions with caloric restriction or resveratrol administration. It is expected of this study mechanistic conclusion for longevity and possible clinical applications in the mechanism of atherosclerosis prevention.

Condition or disease	Intervention/treatment	Phase
Vascular System Injuries; Lipid Metabolism Disorders; Endothelial Disfunction	Drug: Resveratrol; Behavioral: Caloric restriction	Not Applicable

Detailed Description:

After a washout period of 15 days without medication, men and women will be randomized to the group of calorie restriction or resveratrol so that in 24 individuals (12 women and 12 men) will be given a hypocaloric diet (1000 calories per day) and the remaining 24 individuals (12 women and 12 men), a daily pill of 500mg of resveratrol. In the two moments, after the washout period and before the intervention (baseline) and after 30 days of intervention (final) will evaluate the clinical, laboratory and vascular reactivity of all subjects.

Study Design

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	48 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Prevention
Official Title:	Influence of Caloric Restriction and Resveratrol in the Sirtuin System in Women and Men Aged 55 to 65 Years.
Study Start Date :	August 2012
Actual Primary Completion Date :	July 2014
Actual Study Completion Date :	December 2014

Arms and Interventions

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Experimental: men with resveratrol; 12 men will receive a pill with 500mg of resveratrol daily for 30 days	Drug: Resveratrol; 1 pill daily containing 500 mg/d of resveratrol for 30 days
Experimental: women with resveratrol; 12 women will receive a pill with 500mg of resveratrol daily for 30 days	Drug: Resveratrol; 1 pill daily containing 500 mg/d of resveratrol for 30 days
Active Comparator: men with caloric restriction; 12 men will follow a 1000 calories per day diet for 30 days	Behavioral: Caloric restriction; Diet of 1000kcal per day for 30 days
Active Comparator: women with caloric restriction; 12 women will follow a 1000 calories per day diet for 30 days	Behavioral: Caloric restriction; Diet of 1000kcal per day for 30 days

Outcome Measures

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Direct Evaluation of the Sirtuin 1 Gene Expression [ Time Frame: 30 days post-treatment ]
   The Sirtuin 1 gene expression was measured by real time PCR in peripheric blood. Unit of measure was arbitrary unit. "Arbitrary unit was relative to the control gene expression (control gene = 1)".
2. Sirtuin [ Time Frame: 30 days post-treatment ]
   Sirtuin plasma levels before and 30 days post-treatment

Secondary Outcome Measures :

1. Influence of the Sirtuin 1 System on Lipid Profile, Glucose, and C-reactive Protein. [ Time Frame: 30 days post-treatment ]

   For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration:

   - serum HDL, LDL, lipoprotein(a), C reactive protein, glucose.

2. Influence of the Sirtuin 1 System on Apolipoproteins AI and B. [ Time Frame: 30 days post-treatment ]

   For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration:

   - apolipoproteins AI and B

3. Influence of the Sirtuin 1 System on Estradiol [ Time Frame: 30 days post-treatment ]

   For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration:

   - estradiol

4. Influence of the Sirtuin 1 System on Platelet Aggregation. [ Time Frame: 30 days post-treatment ]

   For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration:

   - platelet aggregation by ADP and norepinephrine.

5. Influence of the Sirtuin 1 System on Biomarkers [ Time Frame: 30 days post-treatment ]

   For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration:

   - non-esterified fatty acids, insulin, luteinizing hormone, follicle stimulating hormone.

6. Influence of the Sirtuin 1 System on Estrone and Norepinephrine. [ Time Frame: 30 days post-treatment ]

   For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration:

   - estrone, norepinephrine.

7. Influence of the Sirtuin 1 System on Receptor for Advanced Glycation End Products (RAGE) Gene Expression [ Time Frame: 30 days post-treatment ]

   For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration:

   • RAGE gene expression
   • "Arbitrary unit was relative to the control gene expression (control gene = 1)"
8. Influence of the Sirtuin 1 System on Thromboelastography Clot Formation. [ Time Frame: 30 days post-treatment ]

   For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration:

   -dynamics of clot formation: clot onset time and clot complet

9. Influence of the Sirtuin 1 System on Thromboelastography. [ Time Frame: 30 days post-treatment ]

   For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration:

   - slope of clot formation dynamics

10. Influence of the Sirtuin 1 System on Max Elasticity of Clot on Thromboelastography. [ Time Frame: 30 days post-treatment ]

    For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration:

    -max elasticity of clot on thromboelastography

Other Outcome Measures:

1. Differences Between Men and Women. [ Time Frame: 30 days ]
   We will also compare women vs men baseline and final data.

Eligibility Criteria

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	55 Years to 65 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

• clinical history, physical examination and electrocardiogram normal

Exclusion Criteria:

• premenopausal women (less than 1 year of natural amenorrhea)
• Body mass index ≥ 35 kg/m2
• Smoking
• Severe hypertension (diastolic blood pressure ≥ 110 mmHg)
• Severe dyslipidemia (triglycerides ≥ 500mg/dL, total cholesterol ≥ 300mg/dL)
• Diabetes
• Previous using previous statins or hormone replacement therapy. Other exclusion criteria are: chronic renal failure (serum creatinine ≥ 2.0 mg / dl), hepatic, endocrine, hematologic, respiratory or metabolic clinically significant.

Contacts and Locations

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

Brazil
INCOR - Heart Institute
São Paulo, Brazil, 05403-900

Sponsors and Collaborators

InCor Heart Institute

Investigators

Principal Investigator:	Antônio de Pádua Mansur, PHD	InCor Heart Institute

More Information

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	ANTONIO DE PADUA MANSUR, PHD, InCor Heart Institute
ClinicalTrials.gov Identifier:	NCT01668836 History of Changes
Other Study ID Numbers:	788012; 2012/01051-5 ( Other Grant/Funding Number: FAPESP - SAO PAULO RESEARCH FOUNDATION )
First Posted:	August 20, 2012
Results First Posted:	April 18, 2016
Last Update Posted:	April 18, 2016
Last Verified:	March 2016

Keywords provided by ANTONIO DE PADUA MANSUR, InCor Heart Institute:

sirtuin; atherosclerosis; longevity	calorie restriction; resveratrol; vascular reactivity

Additional relevant MeSH terms:

Resveratrol; Metabolic Diseases; Lipid Metabolism Disorders; Vascular System Injuries; Vascular Diseases; Cardiovascular Diseases; Wounds and Injuries; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents	Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Antimutagenic Agents; Anticarcinogenic Agents